Assessing the Bioactive Profile of Antifungal-Loaded Calcium Sulfate against Fungal Biofilms
| Autor: | Donald Hansom, Phillip A. Laycock, Jason L. Brown, Craig Delury, Mark C. Butcher, Gordon Ramage, Rebecca Wilson-van Os |
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| Rok vydání: | 2021 |
| Předmět: |
Antifungal Agents
medicine.drug_class Antibiotics antimicrobial agents Microbial Sensitivity Tests Calcium Sulfate biofilm joint infections Microbiology 03 medical and health sciences chemistry.chemical_compound Amphotericin B medicine Experimental Therapeutics Pharmacology (medical) Viability assay wound management Fluconazole Candida 030304 developmental biology Pharmacology 0303 health sciences 030306 microbiology Chemistry Broth microdilution Biofilm Antimicrobial Infectious Diseases fungal Biofilms Caspofungin medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Calcium sulfate (CS) has been used clinically as a bone or void filling biomaterial, and due to its resorptive properties have provided the prospect for its use as a release mechanism for local antibiotics to control biofilms. Here, we aimed to test CS beads loaded with three antifungal drugs against planktonic and sessile fungal species to assess whether these antifungal beads could be harnessed to provide consistent release of antifungals at biofilm inhibitive doses. A panel of different fungal species (n=15) were selected for planktonic broth microdilution testing with fluconazole (FLZ), amphotericin B (AMB) and caspofungin (CSP). After establishing planktonic inhibition, antifungal CS beads were introduced to fungal biofilms (n=5) to assess biofilm formation and cell viability through a combination of standard quantitative and qualitative biofilm assays. Inoculation of a hydrogel substrate, packed with antifungal CS beads, was also used to assess diffusion through a semi-dry material, to mimic active infection in-vivo. In general, antifungals released from CS loaded beads were all effective at inhibiting the pathogenic fungi over 7-days within standard MIC ranges for these fungi. We observed a significant reduction of pre-grown fungal biofilms across key fungal pathogens following treatment, with visually observable changes in cell morphology and biofilm coverage provided by scanning electron microscopy. Assessment of biofilm inhibition also revealed reductions in total and viable cells across all organisms tested. These data show that antifungal loaded CS beads produce a sustained antimicrobial effect, which inhibits and kills clinically relevant fungal species in-vitro as planktonic and biofilm cells. |
| Databáze: | OpenAIRE |
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